Osmotic dosage forms are known from U.S. Pat. Nos. 3,845,770; 3,916,899; 4,034,758; 4,077,407; 4,327,725; and 4,783,337. The development of osmotic dosage forms was pioneered by Alza with the development of OROS™, an elementary oral osmotic system. Osmotic dosage forms work on the principle of osmosis and deliver drugs in a near zero order profile. The osmotic dosage forms comprise a core comprising a biologically active ingredient and a semi-permeable membrane covering said core. The semi-permeable membrane, often also called semi-permeable wall, is permeable to the passage of aqueous external fluid, such as gastric or intestinal fluid, and allows the external fluid to permeate the membrane and optionally dissolve the biologically active ingredient. The membrane is substantially impermeable to the passage of the active ingredient in solution or dispersion with the external fluid. An osmotic passageway is provided through the wall to deliver the solution or dispersion of the active ingredient in the external fluid to the environment instead of delivery via diffusion through the membrane. The osmotic dosage forms allow an extended release of an active ingredient. If the osmotic dosage form comprises an active ingredient which is insoluble in the external fluid, the osmotic dosage form often comprises a polymeric swelling agent which expands upon contact with the external fluid and pushes the active ingredient through the passageway. WO 2006/046114 discloses osmotic dosage forms which essentially consist of a core comprising a drug layer and a push layer, a semi-permeable membrane surrounding the core and at least one passageway in the semi-permeable membrane.
The above-mentioned patent publications disclose that materials useful in forming the semi-permeable membrane are cellulose esters, cellulose diesters, cellulose triesters, cellulose ethers, cellulose ester-ethers, cellulose acetate, cellulose diacetate, cellulose triacetate, cellulose acetate proprionate, and cellulose acetate butyrate.
The Chinese Patent publication CN1923184-A discloses osmotic release tablet formulations of venlafaxine hydrochloride, a water soluble drug. The control-release cluster aperture coupled with osmotic pump tablet is composed of a flake core and coating film The coating comprises one or more of film-forming polymers selected from cellulose acetate, ethyl cellulose, hydroxypropyl methylcellulose, and/or polyacrylic resin and further comprises 20 to 45 wt. % of a pore-forming agent, such as sugar, sodium chloride, sorbitol, polyethylene glycol or hydroxypropyl cellulose, based on the weight of the coating. The coating may also comprise a plasticizing agent, such as triethyl citrate, dibutyl sebacate, phthalate ester, and/or polyethylene glycol 4000. Unfortunately, this coating does not have sufficient film strength and may be broken by polymeric swelling agents which are typically included in osmotic release tablets.
The most preferred and well-known semi-permeable membrane material is cellulose acetate. Many commercially used osmotic dosage forms, such as the OROS® Push-Pull™ system developed at ALZA, comprise cellulose acetate as film-forming material for the semi-permeable membrane. In the process for producing the osmotic dosage form a shaped core comprising a biologically active ingredient is typically coated with a starting material for the semi-permeable membrane dissolved in an organic solvent. When the osmotic dosage form comprises cellulose acetate as film-forming material for the semi-permeable membrane, there is a significant lag-time between the intake of the osmotic dosage form by an individual such as a human being, and the onset of the release of the biologically active ingredient. Moreover, cellulose acetate has to be dissolved in acetone for preparing the semi-permeable membrane, which is undesirable for safety reasons.
Several attempts have been made by the skilled artisans to overcome this lag-time. The most common approach is to coat the osmotic dosage form with an external immediate release coating layer that comprises the biologically active ingredient. Unfortunately, such additional external immediate release coating layer adds to the complexity and costs of osmotic dosage forms. Moreover, an external coating layer comprising the biologically active ingredient is often undesirable for product safety reasons.
Accordingly, it would be desirable to provide a new osmotic dosage form which does not comprise cellulose acetate as the film-forming material for the semi-permeable membrane. It would be more desirable to provide a new osmotic dosage form which does not have a significant lag-time between the intake of the osmotic dosage form and the onset of the release of the biologically active ingredient which is experienced with osmotic dosage forms comprising cellulose acetate as the film-forming material for the semi-permeable membrane. It would be particularly desirable to provide a new osmotic dosage form which provides a substantially zero order profile during a time period of 2 to 12 hours after the contact with an aqueous liquid has started. It would also be particularly desirable to provide a new osmotic dosage form that has sufficient film strength such that it is not broken by polymeric swelling agents which are typically included in osmotic dosage forms.